There is good evidence from our laboratory indicating that catecholamines through cAMP (adenosine 3 feet, 5 feet-monophosphate) mediate the induction of the lactate dehydrogenase M subunit in rat 06 glioma cells at the transcriptional level. However, the mechanism whereby cAMP initiates and controls the transcriptional events is as yet unknown, but based on its established effects may involve a mechanism of activation of nuclear cAMP-dependent protein kinase (through nuclear translocation of cytoplasmic cAMP-dependent protein kinase), phosphorylative modification of nucleosomal proteins and other nuclear proteins resulting in a structurally and functionally altered chromatin. The proposed studies are aimed at defining (a) the mechanism of nuclear translocation of cytoplasmic cAMP-dependent protein kinase by biochemical and immunochemical methods; (b) to identify nuclear protein kinase (and phosphatase) substrates and the exact phosphorylation sites; (c) to elucidate the kinetics of phosphorylation/ (dephosphorylation after isoproterenol stimulation; and (d) to functionally correlate these phosphorylation/dephosphorylation events with induction of nuclear lactate dehydrogenase mRNA synthesis after isoproterenol stimulation.